Toxicity 101 – the basics

Dr Fi Dann Ray MSc Applied Toxicology, MSc Chiropractic

September  2018

Given the nature of this site -detoxicology, it seemed useful to outline the general approach to toxins in the medical and scientific literature.

The basics of toxicology are known as ADME, Absorption, distribution, metabolism and excretion. Examining any toxin, or mix of toxins from this framework helps a scientist or clinician to see the impact that substance has on the body.

 

A=  Absorption. How toxins enter the body.

There are basically 4 routes – ingested (our food and drink), inhaled (via the lungs) injected (vaccines for instance) or absorbed via the skin.

Ingested toxins have to get through several layers of the body’s defence – stomach acid, the barrier of the gut lining which rejects many toxins and sends them back into the gut lumen (the inside of the gut ‘tube’ where all the food waiting to be digested is), and then the liver. The blood leaving the gut will be rich in the digested nutrients extracted from our food, but can also contain undesirable toxins. All the blood supply from the gut passes through the liver for screening and some processing of nutrients and toxins before it enters the circulation.     Toxins that make it through the liver then enter the general circulation.

Inhaled toxins also have to get through several layers of the body’s defense.   As with ingested toxins, this route of exposure is familiar to the body so we have mechanisms to deal with it. Firstly we have nasal hairs to trap larger particulate matter, then the lungs themselves are rich is similar enzymes as the ones found in the liver for detoxification. The immune system of the lungs also plays a part in destruction of some types of toxins.   Some toxins cause inflammation in the lungs (tobacco[i]/ Vaping[ii]/ weed smoke[iii], asbestos[iv]), others enter the circulation. Particulate matter from diesel exhaust fumes are inhaled but the major area of effect is the blood vessels and heart rather than the lung[v].

Toxins absorbed through the skin – there are not many of these as the skin is such a good natural barrier. As the skin is rich in fats, most water based (Polar) toxins cannot enter to reach the circulation, and toxins over a certain size are also excluded. Drugs that are designed to be absorbed from a patch through the skin have to be very carefully designed to be able to get through the skin.

Injected toxins. Injection of substances into the body is a route of toxin exposure that we were never designed to deal with. It bypasses all the normal first lines of defense.   For Aluminium for instance, our normal route of exposure is via our food as aluminium is a very common element in the earth’s crust and we are frequently exposed. Gut mechanisms mean that for most people, approx. 0.1% of the aluminium we are exposed to in our diet actually enters the circulation[vi]. Aluminium via injection (in many vaccines) completely bypasses this defense.   Even 3 years after injection, 4% of the injected aluminium was still in the body[vii]. Immune system activation (marcophages[viii] etc)can mean some toxins are transported from the injection site via adjvant monocyte lineage cells and the like, to other parts of the body never normally exposed to significant levels of aluminium, such as lymphoid tissue and the brain[ix].

 

D=Distribution.Where a toxin goes in the body

Where a toxin is distributed to in the body depends of the characteristics of that toxin. Some toxins (many chemical toxins) predominately are found in body fats, other such as mercury bind to proteins[x].   Different toxins tend to accumulate in different organs. Lead for instance is found in higher concentration in bone[xi], cadmium in the liver and kidneys[xii], flame retardant chemicals in body fat[xiii].

 

M=Metabolism – How a toxin is processed or affects the proceses of the body

Once into the circulation toxins can be filtered out by the kidneys, dealt with by the immune system or processed by the liver.   Individual cells also have mechanisms for detecting and removing toxins and undesirable substances from themselves[xiv].

Whilst the toxins are circulating though and depending on their type, they may bind to proteins in the blood, be mistaken for desired nutrients and absorbed and used in cells by mistake, may enter cells by piggybacking onto a desired substance, may become deposited in an area of the body and then cause inflammation or otherwise distributed in the body via the circulation of blood or lymph.

Toxins absorbed into cells and used instead of the desired mineral will disrupt the working of that particular cellular mechanism, increasing, decreasing or distorting its function.

Our experience with mercury, based on blood levels of mercury post amalgam filling removal, is that the level is elevated for 3 days post extraction. So for those 3 days, the circulating mercury may be taken up by brain cells, the thyroid, other body tissues, or dealt with an removed from circulation by the kidney or liver.

 

E= Excretion – How a toxin leaves the body

 The level of toxins within a persons body depends on certain factors. Much of this depends on the ability to excrete the toxins that are absorbed. There is a large variation on this over the population.

  • Generally the more toxins you have been exposed to, the higher the body burden.
  • Age – older people tend to have higher levels of some toxins as they’ve had longer to aquire them
  • Nutritional status – lower levels of various minerals and vitamins can hamper the ability of our detox mechanisms to work as many require selenium[xv] (recycle glutathione) or zinc (metallothionein, alcohol dehydrogenase) for instance. Reduced levels of zinc and selenium in the diet lead to higher retention/ toxicity of many metal toxins in the body.
  • Genetic differences in enzymes. There are many variants of the multitude of enzymes involved in detox (proteins that the body makes that perform a reaction in the body – breaking down food, making substances we need, preparing substances for excretion, making energy from food).   Some of these differences can make a reaction in the body happen too slowly, too fast, to need more of certain vitamins and minerals in the best, most available form, or not happen at all. Some examples (there are many) include:
    1. Apo E4. Reduces the ability to remove metals from brain cells. Associated with a higher risk of Alzheimer’s and coronary heart disease[xvi].
    2. MTHFR – reduced methylation. Heightened need for bioavailable folate (MTHF)[xvii]
    3. COMT – also related to methylation, neurotransmitter metabolism [xviii]
    4. GST – glutathione is a major cellular defence mechanism molecule and can be recycled within the cell
    5. Metallothionines – Neuroprotective. provide zinc for regulation of gene expression, contribute to redox stability of the cell and can bind metal ions[xix].
  • Stress – long term psychological stress depletes the body of nutrients and increases inflammation, leading to a tendency to increase the toxic load
  • EMR exposure. Exposure to wifi has been found to increase the leakage of mercury from amalgam fillings. EMR exposure from cell-phones and wifi at night also affects the body’s ability to do cellular ‘housekeeping’, the cleaning, maintenance and repair that happens as we sleep, particularly in the brain. Diminished repair and cleaning leads to less toxin excretion, more free radicals and so more damage.
  • Damage/ stress to the organs of excretion. An over stressed or damaged liver, whether due to liver disease (fatty liver, alcohol/drug damage, cirrhosis etc) or one already dealing with a high level of toxins/ metabolic stress will struggle to remove as many toxins as it would otherwise.   A leaky gut will allow more toxins into the blood than one that is healthy.
  • Constipation leads to a higher reabsorption of waste substances into the body than would normally happen. This causes increased stress on the liver and reduced ability to excrete toxins.

 

Summary

On an individual basis, differences in the absorption, distribution, metabolism and excretion of different metal and chemical toxins make a huge difference to the effect that they have on the body and mind. There is considerable variation between people for many different reasons.

 

 

References.

[i] Strzelak, A., Ratajczak, A., Adamiec, A., & Feleszko, W. (2018). Tobacco Smoke Induces and Alters Immune Responses in the Lung Triggering Inflammation, Allergy, Asthma and Other Lung Diseases: A Mechanistic Review. International Journal of Environmental Research and Public Health, 15(5), 1033. http://doi.org/10.3390/ijerph15051033

[ii] Scott A, Lugg ST, Aldridge K, et al.  Pro-inflammatory effects of e-cigarette vapour condensate on human alveolar macrophages.  Thorax Published Online First: 13 August 2018. doi: 10.1136/thoraxjnl-2018-211663

[iii] R. M. Maertens, P. A. White, A. Williams, C. L. Yauk. 2013. A global toxicogenomic analysis investigating the mechanistic differences between tobacco and marijuana smoke condensates in vitro.  Toxicology, Volume 308, Pages 60-73, ISSN 0300-483X,.  https://doi.org/10.1016/j.tox.2013.03.008.

[iv] Sayan, M., & Mossman, B. T. (2016). The NLRP3 inflammasome in pathogenic particle and fibre-associated lung inflammation and diseases. Particle and Fibre Toxicology, 13, 51. http://doi.org/10.1186/s12989-016-0162-4

[v] Haiyan Tong, Ana G. Rappold, Melissa Caughey, Alan L. Hinderliter, Donald W. Graff, Jon H. Berntsen, Wayne E. Cascio, Robert B. Devlin & James M. Samet (2014) Cardiovascular effects caused by increasing concentrations of diesel exhaust in middle-aged healthy GSTM1 null human volunteers, Inhalation Toxicology, 26:6, 319-326, DOI: 10.3109/08958378.2014.889257

[vi] Drüeke T.B. 2002. Intestinal absorption of aluminium in renal failure. Nephrol Dial Transplant.;17 Suppl 2:13-6.

[vii] Masson, J., Crépeaux, G., Authier, F., Exley, C., & Gherardi, R. (2018). Critical analysis of reference studies on the toxicokinetics of aluminum-based adjuvants. Journal of Inorganic Biochemistry, 181, 87-95.

[viii] Chkheidze, R., Burns, D., White, C., Castro, D., Fuller, J., & Cai, C. (2017). Morin Stain Detects Aluminum-Containing Macrophages in Macrophagic Myofasciitis and Vaccination Granuloma With High Sensitivity and Specificity. Journal of Neuropathology & Experimental Neurology, 76(4), 323-331.

[ix] Gherardi RK1, Aouizerate J1, Cadusseau J2, Yara S2, Authier FJ3. 2016 Aluminum adjuvants of vaccines injected into the muscle: Normal fate, pathology and associated disease.Morphologie.Jun;100(329):85-94. doi: 10.1016/j.morpho.2016.01.002. Epub 2016 Apr 6.

[x] Kuras, R., Janasik, B., Stanislawska, M., & Wasowicz, W. (2018). Revision of the reciprocal action of mercury and selenium. International Journal of Occupational Medicine and Environmental Health, 31(2013), 1–18. https://doi.org/10.13075/ijomeh.1896.01278

[xi] Fang, F., Peters, T., Beard, J., Umbach, D., Keller, J., Mariosa, D., Allen, K., Ye, W., Sandler, D., Schmidt, S., & Kamel, F. (2017). Blood Lead, Bone Turnover, and Survival in Amyotrophic Lateral Sclerosis. American Journal of Epidemiology, 186(9), 1057-1064.

[xii] Friberg, L. (1983). Cadmium. Annual Review of Public Health, 4(1), 367-367.

[xiii] Pulkrabová, J., Hrádková, P., Hajšlová, J., Poustka, J., Nápravníková, M., & Poláček, V. (2009). Brominated flame retardants and other organochlorine pollutants in human adipose tissue samples from the Czech Republic. Environment International, 35(1), 63-68.

[xiv]

[xv] Xu, L., Zhang, W., Liu, X., Zhang, C., Wang, P., & Zhao, X. (2018). Circulatory Levels of Toxic Metals (Aluminum, Cadmium, Mercury, Lead) in Patients with Alzheimer’s Disease: A Quantitative Meta-Analysis and Systematic Review. Journal of Alzheimer’s Disease, 62(1), 361-372.

[xvi] Godfrey, M., Wojcik, D., & Krone, C. (2003). Apolipoprotein E genotyping as a potential biomarker for mercury neurotoxicity. Journal of Alzheimer’s Disease, 5(3), 189-195.

[xvii] https://draxe.com/mthfr-mutation/

[xviii] http://www.beyondmthfr.com/treating-comt-and-mao-how-comt-influences-the-brain/

[xix] Roos, P., & Dencker, L. (2012). Mercury in the Spinal Cord After Inhalation of Mercury. Basic and Clinical Pharmacology & Toxicology, 111(2), 126-132.